Homoallyl silyl ether

The tandem use of asymmetric allylboration to give enantiomerically pure ho-moallyHc alcohols followed by cross-metathesis of homoallylic silyl ethers with p-substituted styrenes has been reported [120] (Eq. 19). Exclusively trans cross-coupled products were formed in 50-75% yields. 

During the past 2 years several research groups have published research that either uses or expands upon Crowe s acyclic cross-metathesis chemistry. The first reported application of this chemistry was in the synthesis of frans-disubstitut-ed homoallylic alcohols [30]. Cross-metathesis of styrenes with homoallylic silyl ethers 15, prepared via asymmetric allylboration and subsequent alcohol protection, gave the desired trans cross-metathesis products in moderate to good yields (Eq. 15). 

Migratory aptitude, however, highly depends on the bulk of the substituents on silicon131,132, and is opposite to the size of the silyl groups in the order listed in entry 33 of Table l44. As shown in equation 31, homoallylic silyl ethers 65 react with lithium di-ferf-butylbiphenylide to give allylsilanes 66. The trend of migratory aptitude of silyl... 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

Carbonyl compound alkylations. Allylic alcohols and homoallylic silyl ethers are prepared from alkynes and dienes, respectively. 

The a-siloxyalkyl radical intermediate can be used for carbon-carbon bond formation by intra- and intermolecular trapping (Scheme 10.233). In the BUjSriH-mediated system, a bromoalkenoylsilane is efficiently converted into a bicyclic compound by tandem radical cyclization [601]. When allyltributylstannane is used instead of BuaSnH, the a-siloxyalkyl radical generated from a 5-bromoalkanoylsi-lane undergoes homolytic allylation to provide a homoallyl silyl ether [602]. 

Allylation of nascent A-tosylimines is observed when the carbonyl compounds are mixed with TSNH2, SnCl2, and NCS, while chiral homoallylic amines can be obtained from imines in the presence of a ir-allylpalladium catalyst, the advantage being the replacement of allylstannanes with allylsilanes. When YbCl, is used as catalyst the allylation of aldehydes affords homoallyl silyl ethers. ... 

Ni(carbene) species generated in situ have been used to effect the catalytic coupling of dienes and variously substituted benzaldehydes in the presence of HSiEta to give the Z-homoallylic silyl ethers (18) in 5-20 catalytic turnovers (equation 4) it is interesting to note that using PPha analogues of the Ni(0) complexes n = 2) gives the... 

In 2001, Mori and coworkers reported a nickel-NHC-catalyzed system for the reductive coupling of aldehydes and 1,3-dienes that had distinct properties from a nickel-phosphine based system. Both systems generated the homoallylic silyl ether however, use of phosphines resulted in selectivity, while using an NHC reversed selectivity and resulted in the Z isomer (Figure 13.42) [94]. 

Rhodium-catalysed intramolecular hydrosilylation of homoallyl silyl ethers (52), mediated by norbornene, has been shown to be controlled by ligands thus, with bis(diphenylphosphino)hexane (dpph), the reaction produces oxasilacyclohexanes (53), whereas frani-oxasilacyclopentanes (54) are formed in the presence of BINAR Norbornene is believed to serve as a hydride shuttle. " ... 

Pioneering studies of Trost and his co-workers have explored all the parameters of this reaction. An interesting piece of work has, for instance, shown that the presence of an ether or a silyl ether in a substrate also exerts a profound effect on the regioselectivity of the cyclization. Thus, a silyl ether group at the allylic position (202) furnishes the corresponding 1,3-diene 203, whereas an ether group at the homoallylic position gives exclusively the 1,4-diene 205 (Scheme 50).210... 

Suzuki T, Oriyama T (1999) Novel reactions of ethylene acetals with silyl-substituted nucleophiles. A mild and efficient procedure for the synthesis of homoallyl alkyl ethers and unsymmetrical dialkyl ethers. Synth Commun 29 1263-1269... 

Unsaturated 1,5-dicarbonyl compounds. The phenylthioalkylation of silyl enol ethers of carbonyl compounds (9, 521-522) can be extended to the synthesis of unsaturated 1,5-dicarbonyl compounds. In a typical reaction the enol silyl ether of a ketone is alkylated with the unsaturated chloride 1 under ZnBr2 catalysis to give a homoallyl sulfide. Ozonolysis of the methylene group is accompanied by oxidation of the phenylthio group sulfoxide elimination results in an unsaturated 1,5-aldehydo ketone (equation I). Alkylation with 2 results in a methyl ketone (equation II). 

Employing a silyl ether instead of 38 provided a connective assembly of homoallylic ethers. This three-component reaction leads to the formation of homoallylic ethers 45 via activation of carbonyl 6 by Lewis acid 17. The in situ generated oxo-nium cation 43 can then be trapped by the nucleophilic silyl ether 42 affording 44. The new species can then react with allyltrimethylsilane 1, to form the desired ether 45 with subsequent regeneration of the catalyst and loss of TMSOTMS 47 (Scheme 13.16). 

A wide variety of silyl ethers can be employed, leading to functionalized homo-allylic alcohols or ethers. This three-component coupling reaction, which generates in a single operation a range of homoallylic ethers, does not require the initial and independent synthesis of the acetal (or ketal) derived from 6. 

In summary, the SMS reaction is a truly efficient process, possessing a broad scope and applicable to a number of carbonyls, allylsilanes, alcohols (silyl ethers) or amines. Its usefulness has been validated in several total syntheses and demonstrated by the preparation of chiral homoallylic alcohols. During the development of the SMS reaction, Melkafia and Marko [48] realized that the homoallylic alcohol (ether), if connected to an allylsilane, would form novel annelating agents that would lead to tetrahydropyran derivatives via condensation with carbonyl compounds. This reaction was called IMSC for intramolecular Sakurai cydization and will be discussed in the next section. 

Ni alkoxide as a stoichiometric reaction. However, in this reaction the silylnickel alkoxide 76 is formed, and its reductive elimination affords silyl ethers 77 and 78. At the same time, Ni(0) is regenerated to make the reaction catalytic. The formal total synthesis of elaeokanine C (79) was carried out by this reaction [25], Homoallylic alcohol 81 is obtained by the intermolecular reaction of benzaldehyde with the diene 80 and hydrosilane in high regio- and stereoselective manner [26],... 

The C—Si bond formed by the hydrosilation of alkene is a stable bond. Although it is difficult to convert the C—Si bond to other functional groups, it can be converted to alcohols by oxidation with MCPBA or H2O2. This reaction enhances the usefulness of hydrosilylation of alkenes [219], Combination of intramolecular hydrosilylation of allylic or homoallylic alcohols and the oxidation offers regio- and stereoselective preparation of diols [220], Internal alkenes are difficult to hydrosilylate without isomerization to terminal alkenes. However, intramolecular hydrosilation of internal alkenes can be carried out without isomerization. Intramolecular hydrosilylation of the silyl ether 572 of the homoallylic alcohol 571 afforded 573 regio- and stereoselectively, and the Prelog-Djerassi lactone 574 was prepared by applying this method. 

The accelerated rate for alcoholysis with le, which was observed for the 10 % Pd/C catalytic system, was also seen with the Mn(CO)sBr catalyst. Reactions of le with primary, secondary or tertiary alcohols resulted in moderate yields of the corresponding silyl ketals after 2 h (Table 8 and 9). When mono-alkoxy silane from 3-hydroxy butyrate (lg) was treated with homoallyl alcohol in the presence of Mn(CO)sBr as the catalyst under the standard conditions, 76 % of the silyl ketal was obtained. These silyl ethers possess neighboring carbonyl groups that can participate in the reaction by forming a more reactive pentacoordinated silicon center upon addition of the silane to the metal center.. 

Indium-mediated allylation of trialkyl(difluoroacetyl)silane 70 in aqueous media gives homoallylic alcohol 71 exclusively (Scheme 60). Both water and THF are essential for the allylation reaction. It is worth noting that homoallylic alcohol 71 is formed exclusively under these reaction conditions. On the contrary, enol silyl ether 72 is a major product of the fluorinated acylsilanes reaction with other organometallic compounds than indium via a Brook rearrangement and defluorination. Indium-mediated allylsilylation of carbonyl compounds provides a facile route to 2-(hydroxyethyl)allylsilanes. The allene homologs are similarly prepared (Scheme 61).244,244a... 

The reaction of aldehydes 3 with crotyl silanes (e.g. 5) yields 3-methylated homoallylic products such as 6 and 9. Since crotyl silanes are only weak nucleophiles, the carbonyl compound 3 must be activated. This can be done by addition of a Lewis acid (LA) to form the C2ixhony -Lewis acid complex 4. After addition of 5 and aqueous workup, the homoallylic alcohol 6 is obtained. An alkyl-oxo-carbenium ion 8 is available when treating an acetal 7 with acid or when the aldehyde 3 reacts with a silyl ether 10 in the presence of a Lewis or a Brousted acid (multicomponent crotylation). Crotylation of this alkyl-oxocarbenium ion 8 yields homoallylic ethers 9. 

The use of C2-symmetric 1,2- and 1,3-diols as chiral auxiliaries is a reliable method for asymmetric allylation of acetals [382]. Acyclic acetals derived from homochiral 1-phenylethanol undergo the Hosomi-Sakurai allylation with high diastereoselectivity [383]. Tietze et al. have, on the other hand, reported that the TMSOTf-catalyzed successive acetalization-allylation reaction of aliphatic aldehydes with homochiral silyl ethers 123 and allyltrimethylsilane gives the corresponding homoallyl ethers with complete diastereocontrol these ethers can be readily converted into enantiomerically pure homoallyl alcohols without epimerization (Scheme 10.135) [384]. This method is applicable to asymmetric allylation of methyl ketones [385]. 

The carbonyl-ene reaction is a source of homoallylic alcohols, although the scope is somewhat limited. Synthesis of chiral tertiary a-hydroxycarboxylic esters from glyoxyUc esters has been studied, and many metal catalysts of varying degree of effectiveness have been identified. The Ag-catalyzed reaction between enol silyl ethers and a glyoxylic ester is stericaUy controlled by the Pd-SEGPHOS complex. ... 

Koreeda and Hamann have reported the use of silyl tethers in stereocontrolled syntheses of branched-chain 1,4-diols and 1,5-diols [61]. Exposure of (bromomethyl)silyl ethers prepared from the corresponding homoallylic alcohols with Bu SnH in the presence of AIBN allowed smooth conversion to the corresponding cyclic siloxanes, from which diol products were obtained using standard, oxidative cleavage protocols. While monosubstituted olefin 149 selectively underwent 1-endo cyclization, di- and trisubsti-tuted olefins 150 and 151 preferentially reacted through the 6-exo mode with complete stereocontrol, affording the diol products 152 and 153, respectively (Scheme 10-50). 

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